Image-Guided Stereotactic Spine Radiosurgery on a Conventional Linear Accelerator

Stereotactic radiosurgery for spinal metastasis consists of a high radiation dose delivered to the tumor in 1 to 5 fractions. Due to the high radiation dose in a single or fewer treatments, the precision of tumor localization and dose delivery is of great concern. Many groups have published their experiences of spinal radiosurgery with the use of CyberKnife System (Accuray Inc.). In this study, we report in detail our approach to stereotactic spine radiosurgery (SSRS) using a conventional linear accelerator (Varian Trilogy), utilizing the features of kilovolt on-board imaging (kV-OBI) and cone beam computed tomography (CBCT) for image guidance. We present our experience in various aspects of the SSRS procedure, including patient simulation and immobilization, intensity-modulated radiation treatment (IMRT) planning and beam selection, portal dosimetry for patient planning quality assurance (QA), and the use of image guidance in tumor localization prior to and during treatment delivery.     

Predicting neointimal hyperplasia in stented arteries using time-dependant computational fluid dynamics: A review

This paper reviews the recent literature regarding the time-dependant computational fluid dynamics (CFD) analyses of blood flow through implanted coronary stents. The in vivo processes which result in arterial restenosis are identified. The definition and range of the computationally predicted variables which are believed to stimulate the restenosis processes are evaluated. The reviewed literature is subdivided into effect-based in which the effects of altering the flow model are investigated and design-based in which different geometric stent configurations are compared. Finally, conclusions are made regarding the body of work reviewed and recommendations are provided for future work in this field.     

Reduced degeneration of dopaminergic terminals and accentuated astrocyte activation by high dose methamphetamine administration in nociceptin receptor knock out mice

A major pathology of methamphetamine abuse is loss of dopaminergic function due to destruction of dopaminergic terminals, especially in the striatum. This process is accompanied by gliosis by astrocytes and microglia. Here, we evaluated the function of endogenous nociceptin/orphanin FQ in these events using nociceptin receptor (NOP) knockout mice. Wild-type and knockout mice were injected systemically either saline vehicle or 5 mg/kg methamphetamine four times interspersed by 2 h intervals. Three days later, brains were immunohistochemically processed to visualize methamphetamine-induced loss of tyrosine hydroxylase (as a marker of damage to dopamine terminals), glial fibrillary acidic protein (GFAP, as a marker of astrocytes), and ionized calcium-binding adapter molecule 1 (lba-1, as a marker of microglia) in the striatum. Methamphetamine treatment induced an approximately 80% loss of tyrosine hydroxylase-immunoreactivity, and this effect was mildly attenuated in NOP receptor knockout mice. There was a large increase (approximately 15-fold) in GFAP-immunoreactivity in methamphetamine-treated wild-type mice, which was almost two times larger still in NOP receptor knockout mice. In contrast, Iba-1 immunostaining was only modestly increased (approximately 30%) by methamphetamine treatment, and there were no difference between genotypes. Finally, there were no genotype-dependent differences in hyperthermic responses to methamphetamine. These results indicate that endogenous nociceptin/orphanin FQ exacerbates the neurotoxic effects of methamphetamine on striatal dopamine neurons, and suggests this is due in part to an astrocyte-mediated event.     

Modular peptides promote human mesenchymal stem cell differentiation on biomaterial surfaces

Molecular design strategies in biomedical applications often involve creating modular “fusion” proteins, in which distinct domains within a single molecule can perform multiple functions. We have synthesized a new class of modular peptides that include a biologically active sequence derived from the growth factor BMP-2 and a series of hydroxyapatite-binding sequences inspired by the N-terminal α-helix of osteocalcin. These modular peptides can bind in a sequence-dependent manner to the surface of “bone-like” hydroxyapatite coatings, which are nucleated and grown on a biodegradable polymer surface via a biomimetic process. The BMP-2-derived sequence of the modular peptides is biologically active, as measured by its ability to promote osteogenic differentiation of human mesenchymal stem cells. Our study indicates that the modular peptides described here are multifunctional, and the characteristics of this approach suggest that it can potentially be applied to a range of biomaterials for regenerative medicine applications.